Pasireotide Responsiveness in Acromegaly Is Mainly Driven by Somatostatin Receptor Subtype 2 Expression

Ammar Muhammad, Eva C. Coopmans, Federico Gatto, Sanne E. Franck, Joseph A.M.J.L. Janssen, Aart Jan van der Lely, Leo J. Hofland, Sebastian J.C.M.M. Neggers

Research output: Contribution to journalArticle

Abstract

Background: The response to first-generation somatostatin receptor ligands (SRLs) treatment in acromegaly correlates with expression of somatostatin receptor subtype 2 (SSTR2). However, pasireotide shows the highest binding affinity for SSTR subtype 5 (SSTR5). It has been suggested that in acromegaly, SSTR5 expression is better at predicting the response to pasireotide long-acting release (PAS-LAR) treatment than SSTR2 expression. Aim: To investigate in patients with active acromegaly whether response to SRL treatment correlates to PAS-LAR treatment and to what extent SSTR2 and SSTR5 expression are correlated to the response to PAS-LAR treatment. Methods: We included 52 patients from a cohort that initially received SRL treatment, followed by SRL and pegvisomant combination treatment, and finally PAS-LAR treatment. The long-term response to PAS-LAR was evaluated using a PAS-LAR score. In 14 out of 52 patients, somatotroph adenoma tissue samples were available to evaluate SSTR2 and SSTR5 expression using a previously validated immunoreactivity score (IRS). Results: The percentage IGF-I (times the upper limit of normal) reduction, which was observed after SRL treatment, correlated with PAS-LAR response score during follow-up (r = 0.40; P = 0.003; n = 52). After exclusion of SRL-pretreated patients, SSTR2 IRS was positively correlated to PAS-LAR score (r = 0.58; P = 0.039; n = 9), whereas SSTR5 IRS showed no relation (r = 0.35; P = 0.36; n = 9). Conclusions: In a cohort of patients partially responsive to SRLs, the IGF-I-lowering effects of PAS-LAR treatment correlated with the effect of SRL treatment and seemed to be mainly driven by SSTR2 expression instead of SSTR5.

Original languageEnglish
Pages (from-to)915-924
Number of pages10
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number3
DOIs
Publication statusPublished - Mar 1 2019

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Muhammad, A., Coopmans, E. C., Gatto, F., Franck, S. E., Janssen, J. A. M. J. L., van der Lely, A. J., Hofland, L. J., & Neggers, S. J. C. M. M. (2019). Pasireotide Responsiveness in Acromegaly Is Mainly Driven by Somatostatin Receptor Subtype 2 Expression. The Journal of clinical endocrinology and metabolism, 104(3), 915-924. https://doi.org/10.1210/jc.2018-01524